Trials / Active Not Recruiting

Active Not RecruitingNCT02790515

Provision of TCRγδ T Cells and Memory T Cells Plus Selected Use of Blinatumomab in Naïve T-cell Depleted Haploidentical Donor Hematopoietic Cell Transplantation for Hematologic Malignancies Relapsed or Refractory Despite Prior Transplantation

Status: Active Not Recruiting
Phase: Phase 2
Study type: Interventional
Enrollment: 170 (actual)

Sponsor: St. Jude Children's Research Hospital · Academic / Other
Sex: All
Age: 21 Years
Healthy volunteers: Not accepted

Summary

This study seeks to examine treatment therapy that will reduced regimen-related toxicity and relapse while promoting rapid immune reconstitution with limited serious graft-versus-host-disease (GVHD) and also improve disease-free survival and quality of life. The investigators propose to evaluate the safety and efficacy of selective naive T-cell depleted (by TCRɑβ and CD45RA depletion, respectively) haploidentical hematopoietic cell transplant (HCT) following reduced intensity conditioning regimen that avoids radiation in patients with hematologic malignancies that have relapsed or are refractory following prior allogeneic transplantation. PRIMARY OBJECTIVE: * To estimate engraftment by day +30 post-transplant in patients who receive TCRɑβ-depleted and CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen without radiation. SECONDARY OBJECTIVES: * Assess the safety and feasibility of the addition of Blinatumomab in the early post-engraftment period in patients with CD19+ malignancy. * Estimate the incidence of malignant relapse, event-free survival, and overall survival at one-year post-transplantation. * Estimate incidence and severity of acute and chronic (GVHD). * Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.

Detailed description

Blood progenitor cells will be obtained from a partially matched adult family member (donor). After processing and filtration using the CliniMACS device, cells will be infused into participants meeting eligibility criteria. Prior to transplant, participants will receive a conditioning treatment of rabbit ATG, cyclophosphamide, fludarabine, thiotepa, melphalan, and rituximab. Mesna will be given to help prevent side effects of cyclophosphamide. Tacrolimus will be given to help reduce the risk of GVHD. G-CSF will be given after transplant to help the donor progenitor cells make white blood cells faster so that the immune system is better able to fight infection. Blood progenitor cells will be given in two infusions on Day 0 and Day +1. Progenitor cells then move through the blood stream to the bone marrow space where they should begin to grow. Participant blood will be monitored for 100 days to assure that the progenitor cells begin to grow. If the growth is low, additional progenitor cells may be given. Blood tests will be monitored for up to one year to observe how well the donor cells grow and their effect on the infection-fighting system.

Conditions

Interventions

Type	Name	Description
DRUG	Anti-thymocyte globulin (rabbit)	Given intravenous (IV) prior to transplant on Days -14, -13, -12.
DRUG	Blinatumomab	Given by continuous IV infusion at least 2 weeks post-engraftment. Blinatumomab will be given only to patients with CD19+ malignancies.
DRUG	Cyclophosphamide	Given by IV infusion prior to transplant on Day -9.
DRUG	Fludarabine	Given IV prior to transplant on Days -8, -7, -6, -5, and -4.
DRUG	G-CSF	Given IV or subcutaneous (SQ) following transplant on Days 6 and 7.
DRUG	Melphalan	Given IV prior to transplant on Days -2 and -1.
DRUG	Mesna	Given IV prior to cyclophosphamide administration and at approximately 3, 6, and 9 hours after cyclophosphamide infusion.
DRUG	Rituximab	Given IV prior to transplant on Day -1.
DRUG	Tacrolimus	Given oral (PO) or IV beginning prior to transplant on Day -2. The dose will begin to taper at approximately day +60 after transplant in the absence of GVHD. Tacrolimus was used for the first 5 participants enrolled on study. Subsequent participants receive sirolimus.
DRUG	Thiotepa	Given IV prior to transplant on Day -3.
BIOLOGICAL	HPC,A Infusion	Hematopoietic Progenitor Cell, Apheresis (HPC,A) infusion of TCRɑβ+ depleted cells on day of transplant (Day 0) and HPC,A infusion of CD45RA+ depleted cells on Day +1 following transplant.
DEVICE	CliniMACS	The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.
DRUG	Sirolimus	Given orally (PO) starting Day 0. The dose will be tapered off over two weeks starting on Day +42 in the absence of GVHD.

Timeline

Start date: 2016-07-14
Primary completion: 2025-07-01
Completion: 2026-07-01
First posted: 2016-06-06
Last updated: 2025-08-12

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study
FDA-regulated device study

Source: ClinicalTrials.gov record NCT02790515. Inclusion in this directory is not an endorsement.